| id | Study | Lib. in paper | Exposition period | Study type |
Control type |
Tags | OR 95%CI | x1/n1 x0/n0 | no cases | no exposed | ROB | Ref. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S9200 R31918 |
The NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS), 2022 | Major congenital malformations | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.52 [0.80;2.90] C excluded (control group) |
12/423 44/2,333 | 56 | 423 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9201 R31924 |
The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, disease free | Adjustment: No | 2.89 [1.29;6.49] C | 12/423 12/1,201 | 24 | 423 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12697 R47933 |
Alsfouk (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 | Major congenital malformation | during pregnancy (anytime or not specified) | retrospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
5.00 [0.08;316.71] C excluded (control group) |
0/1 2/15 | 2 | 1 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12699 R47935 |
Alsfouk (Phenytoin) (Controls unexposed, sick), 2021 | Major congenital malformation | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
19.00 [0.27;1331.97] C excluded (exposition period) |
0/1 1/30 | 1 | 1 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12850 R48450 |
Thomas (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 | Major congenital malformations | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
3.06 [0.37;25.57] C excluded (control group) |
7/119 1/50 | 8 | 119 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12851 R48458 |
Thomas (Phenytoin) (Controls unexposed, disease free), 2021 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No |
1.64 [0.62;4.33] excluded (control group) |
6/106 11/319 | 17 | 106 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12852 R48462 |
Thomas (Phenytoin) (Controls unexposed, sick), 2021 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: Yes | 1.21 [0.50;2.90] | 7/119 16/340 | 23 | 119 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9247 R32087 |
Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2019 | Fetal malformations | at least 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
0.45 [0.06;3.43] C excluded (control group) |
1/44 20/406 | 21 | 44 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9248 R32088 |
Vajda (Phenytoin) (Controls unexposed, sick), 2019 | Fetal malformations | at least 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 0.80 [0.10;6.61] | 1/44 5/176 | 6 | 44 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9246 R32077 |
Tomson (Phenytoin), 2018 | Major congenital malformation | at least 1st trimester | prospective cohort | exposed to other treatment, sick | Adjustment: No | 2.25 [1.06;4.79] C | 8/125 74/2,514 | 82 | 125 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9272 R32155 |
Bank (Phenytoin) (Mixed indications), 2017 | Major Malformation | during pregnancy (anytime or not specified) excluded | prospective cohort | exposed to other treatment, sick | Adjustment: No |
14.20 [0.23;878.06] C excluded (exposition period) |
0/3 0/36 | 0 | 3 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9198 R31914 |
He (Phenytoin) (Controls exposed to Lamotrigine, sick), 2017 | Congenital malformations | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
2.14 [0.03;131.94] C excluded (control group) |
0/4 0/8 | 0 | 4 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9199 R31916 |
He (Phenytoin) (Controls unexposed, sick), 2017 | Congenital malformations | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
8.71 [0.15;511.85] C excluded (exposition period) |
0/4 0/31 | 0 | 4 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9186 R31763 |
Arkilo (Phenytoin), 2015 | Major malformations | during pregnancy (anytime or not specified) excluded | retrospective cohort | exposed to other treatment, sick | Adjustment: No |
5.22 [0.09;299.04] C excluded (exposition period) |
0/5 0/24 | 0 | 5 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9206 R31948 |
Källén (Phenytoin) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 | Relatively severe malformations | early pregnancy | population based cohort retrospective | exposed to other treatment, sick excluded | Adjustment: No |
2.65 [1.35;5.22] C excluded (control group) |
12/140 37/1,084 | 49 | 140 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9207 R31950 |
Källén (Phenytoin) (Controls unexposed, NOS) (Indications NOS), 2013 | Relatively severe malformations | early pregnancy | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes | 1.84 [0.95;3.21] | 12/140 49,499/1,575,847 | 49,511 | 140 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9225 R32023 |
Bànhidy (Phenytoin), 2011 | Total congenital abnormalities | throughout pregnancy | case control | unexposed, sick | Adjustment: No Matched | 0.61 [0.21;1.82] C | 14/33 12/22 | 26 | 33 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9209 R31953 |
Mawer (Phenytoin) (Controls exposed to Lamotrigine, sick), 2010 | Major malformations | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.06 [0.05;24.77] C excluded (control group) |
0/7 2/37 | 2 | 7 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9210 R31955 |
Mawer (Phenytoin) (Controls unexposed, disease free), 2010 | Major malformations | 1st trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No Matched |
3.30 [0.17;64.87] C excluded (control group) |
0/7 6/285 | 6 | 7 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9211 R31957 |
Mawer (Phenytoin) (Controls unexposed, sick), 2010 | Major malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 2.03 [0.07;55.28] C | 0/7 1/41 | 1 | 7 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9235 R32046 |
Kini (Phenytoin) (Controls unexposed, sick), 2006 | Major malformations | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
0.97 [0.10;9.07] excluded (exposition period) |
1/26 4/101 | 5 | 26 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9212 R31959 |
Meador (Phenytoin), 2006 | Congenital malformations | during pregnancy (anytime or not specified) excluded | prospective cohort | exposed to other treatment, sick | Adjustment: No |
7.46 [0.81;68.50] C excluded (exposition period) |
4/56 1/98 | 5 | 56 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9238 R32056 |
Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 | Major congenital malformation | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.13 [0.33;3.88] C excluded (control group) |
3/82 21/647 | 24 | 82 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9239 R32064 |
Morrow (Phenytoin) (Controls unexposed, sick), 2006 | Major congenital malformation | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 1.04 [0.27;4.02] C | 3/82 8/227 | 11 | 82 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9220 R31990 |
Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 | Major malformations | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No | 34.33 [0.49;2389.88] C | 0/2 0/52 | 0 | 2 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9231 R32035 |
Kaaja (Phenytoin), 2003 | Major malformation | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 2.94 [0.48;17.82] C | 3/124 2/239 | 5 | 124 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9196 R31897 |
Dean (Phenytoin), 2002 | Major congenital malformations | at least 1st trimester | retrospective cohort | unexposed, sick | Adjustment: No | 3.43 [0.58;20.34] C | 4/25 2/38 | 6 | 25 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9202 R31926 |
Holmes (Phenytoin) (Controls unexposed, disease free), 2001 | Major malformations | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, disease free excluded | Adjustment: Yes |
1.90 [0.30;9.20] excluded (control group) |
3/87 9/508 | 12 | 87 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9203 R31935 |
Holmes (Phenytoin) (Controls unexposed, sick), 2001 | Major malformations | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
8.17 [0.42;160.54] C excluded (exposition period) |
3/87 0/98 | 3 | 87 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9204 R31944 |
Hvas (Phenytoin) (Controls unexposed, disease free), 2000 | Major congenital malformations | 1st trimester | retrospective cohort | unexposed, disease free excluded | Adjustment: No |
83.94 [1.66;4238.34] C excluded (control group) |
0/1 280/23,827 | 280 | 1 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9205 R31946 |
Hvas (Phenytoin) (Controls unexposed, sick), 2000 | Major congenital malformations | 1st trimester | retrospective cohort | unexposed, sick | Adjustment: No | 211.00 [1.73;25761.82] C | 0/1 0/106 | 0 | 1 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9227 R32028 |
Canger (Phenytoin), 1999 | Severe malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 0.80 [0.02;41.97] C | 0/31 0/25 | 0 | 31 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9240 R32066 |
Samrén (Phenytoin), 1999 | Major congential abnormalities | at least 1st trimester | retrospective cohort | unexposed, disease free | Adjustment: No Matched | 0.50 [0.10;3.40] | 1/151 29/2,000 | 30 | 151 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9273 R32157 |
Nulman (Phenytoin) (Controls unexposed, NOS) (Mixed indications), 1997 | Malformations (major) | at least 1st trimester | prospective cohort | unexposed (general population or NOS) | Adjustment: No Matched | 1.55 [0.24;9.91] C | 3/34 2/34 | 5 | 34 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9241 R32068 |
Steegers-Theunissen (Phenytoin), 1994 | Major malformations (ICD9 British Paediatric Association System) | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, disease free | Adjustment: No |
2.76 [0.12;62.85] C excluded (exposition period) |
0/8 2/106 | 2 | 8 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9233 R32038 |
Kelly (Phenytoin), 1984 | Major abnormality | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
0.50 [0.03;8.42] C excluded (exposition period) |
1/41 1/21 | 2 | 41 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Total | 15 studies | 1.69 [1.18;2.41] | 49,730 | 1,341 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1: Controls unexposed, disease free) (Indications NOS; 2: Phenytoin) (Controls unexposed, sick; 3: Phenytoin) (Controls unexposed, sick; 4: Phenytoin; 5: Phenytoin) (Controls unexposed, NOS) (Indications NOS; 6: Phenytoin; 7: Phenytoin) (Controls unexposed, sick; 8: Phenytoin) (Controls unexposed, sick; 9: Phenytoin) (Controls unexposed, sick) ; 10: Phenytoin; 11: Phenytoin; 12: Phenytoin) (Controls unexposed, sick; 13: Phenytoin; 14: Phenytoin; 15: Phenytoin) (Controls unexposed, NOS) (Mixed indications;
Asymetry test p-value = 0.6339 (by Egger's regression)
slope=0.3988 (0.3373); intercept=0.2685 (0.5505); t=0.4877; p=0.6339
excluded 9204, 9202, 9238, 9209, 9210, 9206, 9198, 9247, 12697, 12850, 12851, 9200